The adsorption of proteins, such as albumin or other serum proteins onto surfaces, can create a surface layer that can resist further adsorption of other proteins or cells when placed into contact with an albuminized surface. Thus, an albuminized surface, if the albumin is tightly bound, can create a "biocompatible" coating with bloods or other cellular fluids that contain proteins and/or cells would be ideal for uses such as a vascular graft, cardiovascular implants, catheters, extracorporeal cardiovascular devices (hemodialysis, detoxification, and oxygenation), for titre plates used in clinical diagnostic assays, chromatography separations with protein mixtures, and for detoxifying blood or serum from a chemical that can bind to albumin. Albuminized surfaces do not have widespread use because of the inability to create a tightly bound albumin surface wherein only a relatively insignificant amount of albumin can be removed.
There have been many attempts to treat surfaces with a variety of chemical treatments in order to render the surface more receptive to albumin. The simplest technique is to contact an albumin solution with a surface and incubate it for a specified period of time in the hope that some albumin sticks to the surface. Unfortunately, when the surface is washed, not much albumin remains (Cazenave et al., "Capillary perfusion system for quantitative evaluation of protein absorption and platelet adhesion to artificial surfaces," in Proteins At Interfaces, Physiochemical and Biochemical Studies, Amer. Chem. Soc., pp. 537-550 (1977)). Glutaraldehyde cross-linking of albumin was tried to increase the retention of albumin on the surface, but very little improvement was noted (Guidoin et al., "A Compound Arterial Prosthesis: The Importance of Sterilization Procedure on the Healing and Stability of Albuminated Polyester Grafts," Biomaterial 6:122-128 (1985)).
Rumisek et al. ("Heat-Denatured Albumin-Coated Dacron Vascular Grafts: Physical Characteristics And In Vivo Performance," J. Vascular Surgery 4:136-143 (1986)) tried steam autoclaving the albuminized surface, in an effort to create a tighter binding through denaturation of the protein. Although there was an improvement, the albuminized surfaces of Rumisek et al. cannot be considered to be "tight binding."
Eberhart et al. ("Albumin Adsorption and Retention on C18-Alkyl-Derivatized Polyurethane Vascular Grafts," Artificial Organs 11:375-382 (1987)) refers to a method for grafting carbon alkyl chains to the surface to attempt to increase the surface binding of the albumin. The process of Eberhart et al. is designed to provide for a dynamic exchange of absorbed albumin with albumin in solution. Similarly, Gianazza et al., "A General Method for Fractionation of Plasma Proteins: Dye-Ligand Affinity Chromatography on Immobilized Cibacron Blue 83-6A," Biochem. J. 201:129-136 (1982), coupled a dye (Cibacron Blue F3G-A) to hydrophilic supports to allow the dye to complex albumin. Further, Hoffman et al., "Covalent Binding of Biomolecules to Radiation-Grafted Hydrogels on Inert Polymer Surfaces," Trans. Am. Soc. Int. Organs 8:10-16 (1982), refers to a method for immobilizing albumin onto hydrogels by cyanogen bromide activation of the hydroxyl groups. Neither of the methods of Eberhardt et al., Gianazza et al. nor Hoffman et al. results in tight binding of albumin to surfaces.
Another method of Joseph et al. ("Platelet Adhesion to Surfaces Treated with Glow Discharge and Albumin," J. Biomed. Materials Res. 20:677-682 (1986)) refers to a multistep procedure to increase albumin retention on surfaces. The Joseph et al. method adsorbs albumin onto an untreated surface, exposes the albuminized surface to nitrogen plasma, further adsorbs albumin onto the surface, cross-links the twice albuminized surface with glutaraldehyde and then further adsorbs albumin on the surface for the third time. Despite the rather complicated procedure of Joseph et al., the improvements gained in albumin retention on the surface are small.
Sipehia et al., "Enhanced Albumin Binding to Polypropylene Beads Via Anhydrous Ammonia Gaseous Plasma," Biomaterials 7:471-473 (1986), refers to an ammonia gaseous plasma method onto a polypropylene surface to introduce a net positive charge and thereby bind albumin. Since albumin has a net negative charge at physiologic pH, the binding of albumin in Sipehia et al. is presumably through ionic interactions. Although the method of Sipehia et al. does improve albumin binding to the polypropylene surface, it is still not "tight binding" as defined herein.
Accordingly, the ability to tightly bind a serum protein, such as albumin, to a surface to render it biocompatible has been tried with varying procedures. There have been improvements in the ability of albumin to bind to a surface over the simple albumin exposed to a surface method. However, no dramatic improvements resulting in extremely tight binding of albumin or another protein to a surface have been noted.